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Thijs W. van Harten

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2 papers

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YNICL Journal 2025 Journal Article

Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy

Manon R. Schipper
Thijs W. van Harten
Arie-Tjerk Razoux-Schultz
Kanishk Kaushik
Lydiane Hirschler
Sabine Voigt
Ingeborg Rasing
Emma A. Koemans

Enlarged perivascular spaces (PVS) in the centrum semiovale are an important marker of Cerebral Amyloid Angiopathy (CAA) and are thought to reflect brain clearance dysfunction. However, the current golden standard for assessing PVS is limited to a unilateral, single slice, qualitative analysis, which has the disadvantage of a strong ceiling effect. We aim to introduce a whole-brain PVS volume fraction (PVSvf) measurement to assess cross-sectional and longitudinal PVSvf differences between pre-symptomatic and symptomatic Dutch-type CAA (D-CAA) mutation carriers and similar-age controls. PVSvf was assessed with a Frangi-vesselness filter-based, segmentation tool developed in-house and was compared cross-sectionally in 70 participants (28 symptomatic D-CAA, 17 pre-symptomatic D-CAA, 10 controls > 50 years, 17 controls ≤ 50 years) and longitudinally in 40 participants (16 symptomatic D-CAA, 13 pre-symptomatic D-CAA, 11 controls combined from both age groups). We found a higher baseline PVSvf in symptomatic D-CAA compared to controls ≤ 50 years (p < 0. 0001, 95% CI [−0. 051, −0. 025]) and controls > 50 years (p < 0. 0001, 95% CI [-0. 042, −0. 016]), in pre-symptomatic D-CAA compared to controls ≤ 50 years (p = 0. 023, 95% CI [−0. 035, −0. 002]), and in controls > 50 years compared to controls ≤ 50 years (p < 0. 001, 95% CI [0. 004, 0. 014]). We found no group differences in PVSvf change over time. The introduction of this quantitative measure of PVS volume in D-CAA showed cross-sectional differences already in pre-symptomatic D-CAA, indicating increased PVSvf in the early stages of D-CAA. We did not observe longitudinal differences over a four-year follow-up when analyzed at group level.

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YNICL Journal 2023 Journal Article

Subarachnoid CSF hyperintensities at 7 tesla FLAIR MRI: A novel marker in cerebral amyloid angiopathy

Emma A. Koemans
Marianne A.A. van Walderveen
Sabine Voigt
Ingeborg Rasing
Thijs W. van Harten
Hine J.A van Os
Nelleke van der Weerd
Gisela M. Terwindt

BACKGROUND: We observed subarachnoid cerebrospinal fluid (CSF) hyperintensities at non-contrast 7-tesla (T) fluid-attenuated inversion recovery (FLAIR) MRI, frequently topographically associated with cortical superficial siderosis (cSS), in participants with cerebral amyloid angiopathy (CAA). To systemically evaluate these CSF hyperintensities we investigated their frequency and anatomical and temporal relationship with cSS on 7T and 3T MRI in hereditary Dutch-type CAA (D-CAA), sporadic CAA (sCAA), and non-CAA controls. METHODS: CAA participants were included from two prospective natural history studies and non-CAA controls from a 7T study in healthy females and females with ischemic stroke. CSF hyperintensities were scored by two independent observers. RESULTS: We included 38 sCAA participants (mean age 72y), 50 D-CAA participants (mean age 50y) and 44 non-CAA controls (mean age 53y, 15 with stroke). In total 27/38 (71 %, 95 %CI 56-84) sCAA and 23/50 (46 %, 95 %CI 33-60) D-CAA participants had subarachnoid CSF hyperintensities at baseline 7T. Most (96 %) of those had cSS, in 54 % there was complete topographical overlap with cSS. The remaining 46 % had ≥1 sulcus with CSF hyperintensities without co-localizing cSS. None of the healthy controls and 2/15 (13 %, 95 %CI 2-41, 100 % cSS overlap) of the stroke controls had CSF hyperintensities. In 85 % of the CAA participants CSF hyperintensities could retrospectively be identified at 3T. Of the 35 CAA participants with follow-up 7T after two years, 17/35 (49 %) showed increase and 6/35 (17 %) decrease of regional CSF hyperintensities. In 2/11 (18 %) of participants with follow-up who had baseline CSF hyperintensities without overlapping cSS, new cSS developed at those locations. CONCLUSIONS: Subarachnoid CSF hyperintensities at 7T FLAIR MRI occur frequently in CAA and are associated with cSS, although without complete overlap. We hypothesize that the phenomenon could be a sign of subtle plasma protein or blood product leakage into the CSF, resulting in CSF T1-shortening.

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